Reconciling Conflicting Models for Global Control of Cell-Cycle Transcription

How the program of periodic cell-cycle transcription is controlled has been debated for several years. Models have ranged from control by a CDK-APC/C oscillator, by a transcription factor (TF) network, or by coupled CDK-APC/C and TF networks. In contrast to current models, a recent study concluded that the cell-cycle transcriptional program is primarily controlled by a CDK-APC/C oscillator with little input from the TF network. This conclusion was largely based on an assumption that substantial drops in transcript levels of network TFs would render them unable to regulate their targets. By combining quantitative modeling and an unbiased analysis of the RNA-seq data, we demonstrate that the data from this recent study are completely consistent with previous reports indicating a critical role of a TF network. Moreover, we report substantial transcript dynamics in cells arrested with intermediate levels of B-cyclins, further supporting the model in which oscillating CDK activity is not required to produce phase-specific transcription.